Activation of neuropeptide Y1 (NPY1) receptors in limbic regions produces anxiolysis. It has been demonstrated that some NPY pathways exhibit a sexual dimorphism and modulation by steroids. Stress responses, as well as hormone responses to stress, also display a sex difference as well as a modulation by steroids in both animal and human studies. These findings are of importance since the clinical incidence of anxiety and panic disorders is highest within the female population. The long range objective of this grant proposal is to examine the involvement of central neuropeptide Y (NPY) systems in stress responses in both male and female rats. The specific aims of this proposal are to determine (1) whether a sex difference exists in the expression of NPY and NPY1 receptors in male and female rats, (2) whether male and female animals subjected to stress exhibit similar changes in NPY peptide or receptor expression, and (3) whether NPY receptors in the hypothalamus and amygdala are involved in the regulation of stress-induced behavior or corticosterone secretion. Receptor radioligand slice binding, radioimmunoassay and in situ hybridization will be used to measure changes in NPY receptor expression and NPY peptide and gene expression in the brains and pituitaries of male and female rats before and after stress. The third specific aim will be accomplished by examining changes in basal and stress-induced corticosterone secretion after injection of NPY and NPY1 agonists and antagonists into the hypothalamus and amygdala. These studies will elucidate some of the stress-induced neurochemical changes that occur with respect to NPY systems in male and female animals and contribute potentially important information on the influence of sex steroids in modulating the responses of central NPY systems to stress. These studies will provide insight to the etiology of sexually dimorphic stress responses and another mechanism by which anxiolytic drugs may act on the CNS.